LA JOLLA Richard A. Lerner made his scientific reputation by unraveling novel characteristics and uses of antibodies, helping invent new tools in the process. Upon stepping down as president of The Scripps Research Institute at the beginning of 2012, Lerner didn't walk out the building with a golden test tube or petri dish. The self-proclaimed lab rat continued his work on his great scientific love, and has contributed to a remarkable series of papers of antibodies establishing their virtuosity in various cellular processes.

Among the Lerner team's findings this year alone: Antibodies can convert bone marrow stem cells directly into neural progenitor cells; and they can mimic the effects of different chemicals such as the blood-clotting hormone thrombopoietin, or TPO.

The latest finding, published in the Proceedings of the National Academy of Sciences, is that antibodies can convert stem cells into dendritic cells. These dendritic cells are immune system cells process fragments of protein that aren't part of the body and present them to other immune cells, so they recognize it as foreign.

The paper was published on Aug. 26, two days before Lerner's 75th birthday. Lerner was senior author on this paper, as he was on the first two. Kyungmoo Yea of the Scripps Korea Antibody Institute was first author.

Antibodies are best known for their infection-fighting role -- the body makes them in astronomical configurations, some of which by chance will bind to a molecular target. Lerner's work demonstrates that this conception grossly underestimates the versatility of antibodies.

Earlier in his career, Lerner helped develop methods of generating large libraries of antibodies, which could then be screened for utility. His work led to the discovery of Humira, which treats autoimmune diseases such as rheumatoid arthritis.

Humira blocks TNF from binding to receptors, thus inhibiting inflammation associated with some autoimmune diseases. But antibodies are more than just antagonists that block receptor activity, they are also agonists that turn on receptors. That's what the paper about the TPO agonist showed.

In the new paper, Lerner, Yea and colleagues extend this principle to describe a method for finding antibodies that act ac agonists to control stem cell fate, or what mature form a stem cell will ultimately take. The team inserted "libraries" of antibody genes into TF-1 erythroblasts using lentiviruses, which incorporate their genes into the genome of the host cell. The cells then express the antibody genes, and produce a range of antibodies, which have varied effects on the cells.

As the paper described the method, "each cell becomes a selection system unto itself." As for what to select, in this study, it was shape.

These cells were grown in colonies in soft agar, and their structures observed. Those with interesting shapes different from control cells were examined, and their antibody genes extracted. They then chose three antibodies for further study because they came from colonies with the most interesting shapes. The choice was arbitrary.

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Antibodies turn stem cells into immune cells

Sep. 1, 2013 Stem cell therapy used to regenerate injured tissue in the heart restores synchronous pumping, shows research published today [1 September] in The Journal of Physiology. The study proposes a novel strategy of 'biological resynchronisation' in which stem cells repair heart muscle damage to reestablish correct cardiac motion.

Heart attacks limit local oxygen, which can kill areas of cardiac tissue -- called 'infarcted' areas -- and also leave scarring. This damage leads to a lack of synchrony in the heart beat motion.

Current therapies use pacing devices, but these require healthy tissue for optimal outcome, meaning a third of patients do not respond well to this treatment. However, this new approach discovered by a team at Mayo Clinic in Rochester, Minnesota, USA overcomes this limitation as stem cells actually form functional cardiac tissue and reconstruct heart muscle.

Professor Andre Terzic, who led the study, explains the importance of this potential new therapy: "Heart chambers must beat in synchrony to ensure proper pumping performance. Damage to the heart can generate inconsistent wall motion, leading to life-threatening organ failure.

"The heart is vulnerable to injury due to a limited capacity for self-repair. Current therapies are unable to repair damaged cardiac tissue. This proof-of-principle study provides evidence that a stem cell-based regenerative intervention may prove effective in synchronizing failing hearts, extending the reach of currently available therapies."

Doctor Satsuki Yamada, first author of the study, further explains how the research was carried out:

"Stem cells, with a capacity of generating new heart muscle, were engineered from ordinary tissue. These engineered stem cells were injected into damaged hearts of mice. The impact on cardiac resynchronization was documented using high-resolution imaging."

The observed benefit, in the absence of adverse effects, will need to be validated in additional pre-clinical studies prior to clinical translation.

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Harmonizing a broken heart: Stem cells keep cardiac beat in synchrony

MIAMI -

Each year, 700,000 people suffer a stroke in the United States. Until now, the only recovery for paralysis brought on by the stroke was lengthy rehabilitation.

Now, a new stem cell therapy is helping stroke patients move again.

James Anderson is a triathlete and physical education teacher who was visiting Florida from Maine when suddenly, "I started to feel a little dizzy a little tingling in my right hand and ah I ended up having a stroke," he said.

Anderson did not respond to clot-busting medication or blockage treatments. So, he became paralyzed on the left side of his body.

Dr. Dileep R. Yavatal, a neurologist, treated him as part of a clinical trial in which some of the patients were treated with their own stem cells.

While Anderson doesnt know if he was injected with his own stem cells, two months after treatment, Anderson said, "I have had more movement and strength in my legs."

For the clinical trial, stem cells must be injected into the brain no later than two weeks after the stroke occurs.

Anderson is now able to move around with a walker during rehab and hopes to be able to compete in a triathlon again.

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Health Beat: Stem cells and stroke